Anthelmintic compositions and methods of using same



United States Patent 3,340,144 ANTHELMINTIC COMPOSITIONS AND METHODS OFUSING SAME Henry Martin, Base], Pan] Schmidt, Therwil, and Max Wilhelm,Allschwil, Switzerland, assignors to Ciba Corporation, New York, N.Y., acorporation of Delaware No Drawing. Filed Jan. 19, 1965, Ser. No.426,685 Claims priority, application Switzerland, Apr. 2, 1962, 3,969/62 15 Claims. (Cl. 167-53) in which R represents a substituted orunsubstituted aromatic radical and X stands for oxygen or sulfurinconjunction with a pharmaceutical excipient. By virtue of the effectreferred to above the new preparations are suitable for use by mammalsas medicaments for the treatment of attacks by worms, more especiallytape worms, for example those mentioned :above, or by oxyur-idae.

As excipient there may be used the conventional substances, moreespecially those which are suitable for enteral administration, forexample water, gelatin, lactose, starches, magnesium stearate, talc,vegetable oils, benzyl alcohols, gums, polyalkylene glycols, cholesterolor other known medicinal excipients. The preparations may be, forexample, tablets, capsules, dragees, powders or suppositories, or inliquid form solutions (suitable, for example, for subcutaneous orintravenous injection), suspensions or emulsions. They may be sterilizedand/or may contain assistants such as preserving, stabilizing, wettingor emulsifying agents, or substances for modifying the taste, aroma orcolor. They may also contain further medicinally valuable substances.More especially, by adding a laxative lubricant (for example paraflinoil or castor oil) the removal of the Worms killed or damaged by theaction of the preparation may be accelerated.

The new preparations are advantageously used in the form of tablets,dragees or capsules which contain, for example, 25 to 2000 mg,especially 100-500 mg. of the carbanilide per dosage unit. The dailydose varies according to the nature and special circumstances of theindividual case; it amounts for example to 25 to 2000 mg, ordinarily 1-2g. It is of advantage to extend the treatment over several days, withparticular advantage for 3 days.

The carbanilides preferably used in the aforementioned preparationscorrespond to the general Formula I in which R represents a substitutedor unsubstituted phenyl radical and X stands for oxygen or sulfur, andamong these compounds those deserve special mention which correspond tothe general formula X CF;

bromine or iodine atom, the group OH, SCN, CF

in which R represents an alkyl or alkoxy group, such as a lower alkyl orlower alkoxy group, a fluorine, chlorine, bromine or iodine atom, or thegroup CF NO CN, 4O H, SO NH SO CH OH, SCN, SO NHA /A SO2N\ COOM, COCHCOOA, CONH CONHA or CONA in which A stands for an alkyl group,preferably a lower alkyl group, n is a whole number from 1 to 4, and Xstands for oxygen or sulfur.

Especially valuable is the 3:5-bis-trifluoromethyl-4'nitrocarbanilideand the corresponding thiocarbanilide of the formula I CF;

wherein X stands for O or S.

As further examples of compounds of the general Formula I there may bementioned:

Carbanilides of the general formula 0 a lh l (L l 0 F3 R3 in which R Rand R are identical or different and each represents an alkyl or alkoxygroup, a fluorine, chlorine, bromine or iodine atom, the group CF -NOCN, SO H, S0 NH SO CH SO NHA, OH, -SCN /A SO5N\ -COOH, COOA, CONH CONHAor CONA in which A stands for a lower alkyl group and X for oxygen orsulfur; Carbanilides of the general formula a v R] i V V V in which R RR and X have the above meanings;

Carbanilides of the general formula I X 0 Fa it:

in which R and R are identical or different and each represents an alkylor alkoxy group, a fluorine, chlorine,

NO CN, SO H, SO NH SO CH /A SO2N\ 3 SO NHA, COOH, COOA, CONH2, CONHA orCONA, in which A stands for a lower alkyl radical and X for oxygen orsulfur;

Carbanilides of the general formula in which R R and X have the abovemeanings; Carbanilides of the general rormula Fa r B1 in which R R and Xhave the above meanings;

Carbanilides of the general formula I 1 I CF; I R:

in which R R and X have the above meanings; Carbanilides ofthegeneral-formula in which R R and X have the above meanings;

Carbanilides of the general formula V QW M in which R represents analkyl or alkoxy radical, a 11 orine, chlorine, bromine, or iodine atom,the group CF --CN, SCN, SO H, SO NH SO CH COCH3, SO NHA /A SOs-N 7 COOH,COOA, CONH CONHA or CONA';

in which A stands for a lower alkyl radical and X for oxygen or sulfur;

Carbanilides of the general formula Gr g- Q in'which R and K have theabove meanings, for example the compounds of the formulae S V C b) CF; 7

s C F 7 OF; S 51 The carbanilides to be used in the present-inventioncan be made by known methods. Quite generally, the

compounds are obtained, for example, by reacting the parent materials ofthe general formulae and the two symbols A and B always being so chosenthat v they react together with formation of a urea or thiourea bridge,and R and n have the. meanings definedabove in' the case of the generalFormula II. The reaction may be performed, for example, by reacting acompound of the general formula (in which X stands for oxygen of sulfur)with a compound of the general formula (in which R represents asubstituted or unsubstitutedaromatic radical); or by reacting a compoundof the general formula with a compound of the general formula V 7R--VN=C=X V in which R and X have the above meanings. I

In manufacturing the compounds of the invention 3:5

bis-trifluoromethylphenyl is-ocyanate is reacted, for example, with oneof the following compounds: Aniline or sub stituted anilines such, forexample, as p'arachloraniline, 3 :4-dichloraniline, 3 :S-dichloraniline,2: S-dichloraniline, 3 :4:5 trichloraniline, 224:5 trichloraniline,3-chloro-4- bromaniline, 3-chloro-4-methoxy-aniline,3-ch1oro-4-methylaniline, 3 trifluoromethyl aniline,Z-chlord-S-trifluoromethylaniline, 3 trifluoromethyl 4-chloraniline,bis-3:5-

A trifluoromethylaniline, -4-bromaniline, 2:4-dich1oraniline,

4 aminobenzene sulfonylamide, 4 aminobenzoic acid methyl ester,4-butoxyaniline, 4-thiocyananiline, 4-aminoacetophenone,4-aminophenylacetic acid methyl ester, 3-bromaniline,4-chloro-3-methylaniline, 4-chloro-2-methylaniline, 3:5 dichloro4-methylaniline, 4-chloro-3 :5-dimethylaniline; hydroxyaminobenzenessuch, for example, as 4-chloroor S-chloroor4:5-dichloro-2-amino-1-hydroxybenzene, 3 :4: 6 trichloro 2amino-l-hydroxybenzene, 4- or S-bro-mo-Z-amino-l-hydroxybenzene,4:6-dibromoor 4:6-dichloro-2-amino-l-hydroxybenzene, 4:5-dibromo-Z-amino-l-hydroxybenzene, or4-chloro-3-tn'fluoromethyl-Z-amino-l-hydroxybenzene.

Alternatively, bis-3:S-trifluoromethylaniline is reacted with a phenylisocyanate or isothiocyanate, for example with one that contains one orseveral nitro groups, such as 4-nitrophenyl isocyanate, 3-nitroorZ-nitro-phenyl isocyanate, 4-methyl-3-nitrophenyl isocyanate,4-chloro-3- nitrophenyl isocyanate, 2-nitro-4-chlorophenyl isocyanate,2-methyl-4-nitro-5-chlorophenyl isocyanate, 2-methoxy-4-nitro-S-chlorophenyl isocyanate, or 2:4-dinitrophenyl isocyanate.

The new pharmaceutical preparations may, for example, have thecompositions described in the following examples:

Example 1 3:S-bis-trifiuoromethy1-4'-nitrocarbanilide or thiocarbanilide500.0 Starch 31.0 Colloidal silicic acid 30.0 Gelatin 5.0 Arrowroot 35.0Magnesium stearate 4.0 Talcum 20.0

From the above ingredients split-type tablets of the above composition,Weighing 625 mg. each, are made in usual manner.

Example 2 3:5 bis trifluoromethyl 4'-nitrocarbauilide or thiocarbanilide200.0 Lactose 207.0 Potato starch 182.0 Colloidal silicic acid withhydrolysed starch 10.0 Glycerine 1.5 Magnesium stearate 4.5 Talcum 20.0

From the above ingredients split-type tablets of the above composition,weighing 625 mg. each, are made in usual manner.

Example 3 3 :5-'bis-trifluoromethyl-3'-nitrocarbanilide; M.P. 230-- 3 5-bis-trifiuoromethyl-3-nitro-4'-methylcarbanilide;

M.P. 215-217 C.

3 :5-bis-trifluoromethyl-4'-bromocarbanilide; M.P. 224- 225 .5 C. (onrecrystallization from acetonitrile) 6 3:S-bis-trifluoromethyl-4'-chlorocarbanilide; M.P. 214.5-

215.5 C. (on recrystallization from acetonitrile) 35-bis-trifluoromethyl-3' 5 '-dichloroc arbanilide; M.P.

219-2195 C. (on recrystallization from acetonitrile)S-bis-trifluoromethyl-4'-fluorocarbanilide; M.P. 213- 214 C. (onrecrystallization from acetonitrile) S-bis-trifiuoromethyl-Z' 4 5'-trichlorocarbanilide;

melts on recrystallization from acetonitrile at 227-228 C., thensolidifies again at 229 C. and sublimes at 270-:S-bis-trifluoromethyl-4'-n-butoxycarbanilide; M.P. 195- 195.5 C. (onrecrystallization from acetonitrile) 5-bis-trifluoromethyl-3-chloro-4-methylcarb anilide;

M.P. 230231 C. (on recrystallization from acetonitn'le) 3'S-bis-trifluoromethyl-6-chlorocarbanilide; M.P. 225- 226 C. (onrecrystallization from acetonitrile) :S-bis-trifluoromethyl-Z'4'dichlorocarbanilide M P. 192,-194 C. (on recrystallization fromacetonitrile) 5-bis-trifiuoromethyl-2' 5-dichlorocarb-anilide; M.P.

225.5227 C. (on recrystallization from acetonitrile):5-bis-trifluoromethyl-3'-chlorocarbanilide; M.P. 175- 176 C. (onrecrystallization from acetonitrile):5-bis-trifluoromethyl-3'-bromocarbanilide; melts on recrystallizationfrom nitromethane and washing with chloroform at 174-175 C.

:5 -'bis-trifiuoromethyl-3 4'-dimethylcarbanilide; M.P. 185 .5l86.5 C.(on recrystallization from acetonitrile).

Furthermore, the following compounds may be prepared as described below:

(1) A solution of 16.2 grams of 3:4-dichloroaniline in 150 cc. ofacetonitrile is mixed with a solution of 25.5 grams ofbis-3:5-trifluoromethylphenyl isocyanate (boiling at 63 C. under 14 mm.Hg pressure) in 25 cc. of acetonitrile with vigorous stirring. After ashort time the condensation product of the formula I O l C 3 Cl settlesout. Another 25 cc. of acetonitrile are added and the batch is stirredfor a few hours longer. The3:5-bistrifluoromethyl-3':4"-dichlorocarbanilide is suctioned off,Washed with acetonitrile and dried under vacuum. Crude yield: 36 grams.The product melts at 223-224 C. and, after recrystallization fromacetonitrile, at 227 C.

(2) A solution of 19.5 grams of 4-chloro-3-trifluoromethylaniline in 150cc. of acetonitrile is mixed with a solution of 25.5 grams ofbis-3:S-trifluoromethylphenyl isocyanate in 25 cc. of acetonitrile withvigorous stirring.

Condensation takes place with slight heating up, but no precipitateforms. Evaporation under vacuum yields thetri-3:3:S-trifluoromethyl-4-chlorodiphenyl urea in the form of an oilwhich solidifies soon. The crude product melts at 178-l82 C.; theproduct recrystallized from chlorobenzene melts at 177-178 C. Thecondensation may alternatively be performed in chlorobenzene, whereuponthe urea settles out spontaneously in crystalline form.

(3) A solution of 22.9 grams of bis-3:5-trifluoromethyl-aniline in cc.of acetonitrile is mixed with vigorous stirring with a solution of 25.5grams of bis-3:5-trifluoromethylphenyl isocyanate in 20 cc. ofacetonitrile. The temperature rises to 32 C., but the solution remainsclear. The condensation may alternatively be carried out without asolvent, by heating the reactants as they are on trifluoromethylphenylisocyanate with the calculated amount of Water in acetonitrile.

a water bath. The product is ground in benzene and suc-' (4) A solutionof 19.32 grams of trifluoromethylaniline in 150 cc. of acetonitrile ismixed with a solution of 30.5 grams of bis-3:5-trifluoromethylphenylisocyanate in 30 cc. of acetonitrile. After 2 hours the solvent isevaporated under vacuum and the crude product is recrystallized fromchlorobenzene; it melts at l65l67 C.

(5) 3:S-bis-trifluoromethylphenyl isocyanate is run into a solution of17.75 grams of 3-chloro-4-methoxyaniline ,(ortho-chloro-para-anisidine)in 100 cc. of acetonitrile. The reaction mixture heats up to 42 C., and3:5- bis-trifluoromethyl-3-chloro-4'-methoxycarbanilide settlespartially out. The condensation product is recrystallized fromacetonitrile; it melts at 1=88-190 C.

. (6) 22.9 grams of 3:S-bis-trifluoromethylaniline are mixed with 18.9grams of finely powdered 2-chloro-4- nitrophenyl isocyanate and themixture is heated on a water bath, with the reaction mixture turningsolid, accompanied by a strong evolution of heat. The condensationproduct is powdered, taken up with benzene and the residue is dried.Crude yield: 40 grams. on recrystallization from acetonitrile withaddition of animal charcoal3:S-bis-trifluoromethyl-Z-chloro-4-nitrocarbanilide is obtained inalmost colorless, radially arranged, long needles melting at 222-212 c.

(7) A solution of 16.2 grams of 3:4-dichloraniline in a small amount ofacetonitrile is added to 27 grams of 3:5- bis-trifiuoromethylphenylisothiocyanate (boiling at 83 C. under 12 mm. Hg pressure). The reactionmixture heats'up to 82 C. within a short time; it is kept for 1 hour ona boiling water bath then evaporated under vacuum, whereupon3:5-bis-trifluoromethyl 3'14 dichlorothiocarbanilide is obtained as asolid substance which is recrystallized from' benzene. The purifiedproduct melts at 138-139" C. In an analogous manner the followingcompounds are obtained:

3 :5 -bis-trifluoro-2' 3 '-dichlorocarbanilide; M.P. 222.5- 2235 C. (onrecrystallization from acetonitrile) 3 :5 35-bis-trifluoromethyl-4'-tertiary butylcarbanilide;

M.P. 167-168 C.

3 5-bis-trifluoromethyl-4'-thio cyan-thiocarbanilide;

M.P. 122 C.

(8) 27.1 grams of 3:S-bis-trifluoromethylphenyl thioisocyanate are addedto a solution of 19.5 grams of 3- amino-6-chlorobenzotrifluoride in 20cc. of acetonitrile, and the whole is kept for 1 hour on a'water bath.The reaction mixture slightly changes color and turns thickly liquid; itis evaporated under vacuum and then heated for 2 hours at 90 C. Thesolid crude product melts at 139- 141 C. It is heated in a littlebenzene mixed with animal charcoal, filtered, and the warm solution ismixed with an equal volume of cyclohexane, whereupon3:3'z5-bistrifluoromethyl-4'-chlorothiocarbanilide crystallizes out; itmelts at 1385-139 C.

(9) A solution of 16.5 grams of para-aminobenzoic acid ester in 100 cc.of acetonitrile is stirred with a solution of 25.5 grams of3:S-bis-trifluoromethylpheriyl isocyanate in 20cc. of acetonitrile. Thecondensation product settles out after a few minutes; it is left toitself overnight, then suctioned off and dried under vacuum at 60 C.Crude yield: 39 grams. Melting point: 230-231 C. On crystallization fromabout 500 cc. of acetonitrile, 3 :5-

bis-trifluoromethyl-4'-carb0xy-ethylcarbanilide melts at (10) Bis3:3':S-trifiuoroinethyl-thiocarbanilide is prepared as described aboveunder (9). The crude product is dissolved in hot benzene, treated withanimal charcoal, filtered, and the clear solution is mixed with an equalvolume of cyclohexane, whereupon crystals are obtained which melt at133-134 C.

3 z5-bis-trifluoromethyl-4'-bromo-thiocarbanilide is prepared in acorresponding manner; on recrystallization from -benzene+cyclohexane itmelts at 163164 C.

(11) A solution of 17.1 grams of para-aminophenylmethyl sulfone in 100cc. of acetonitrile is mixed with a solution of 25.5 grams of3:S-bis-trifluoromethylphenyl isocyanate in 20 cc. of acetonitrile.While stirring the batch vigorously, the temperature is maintained at 65C., whereupon 3:5 bis trifluoromethyl-4'-methyl-sulfocarbanilidecrystallizes out overnight; it is recrystallized from acetonitrile andmelts then at 224-225 .5 C.

(12) Without using a solvent, 27.1 grams of3:5-bistri-fluoromethylphenyl isothiocyanate are mixed with 22.9 gramsof 3:5-bis-trifluoromethylaniline, and the whole is heated on a boilingwater bath. The reaction mixture solidifies and forms a solidcrystalline cake. On recrystallization from nitromethane and washingwith benzene, 3:3':5:5'- tetratrifluoromethyl thiocarbanilide melts at184.5- 186 C.

(13) 17.2 grams of sulfanilamide aredissolved with slight heating in 180cc. of acetonitrile, and a solution of 25.5 grams of3:5-bis-trifluoromethylphenyl isocyanate in 25 cc. of acetonitrile isthen vigorously stirred in. The

reaction mixture slowly heats up to 45 C. It is then maintained for 3hours at 65 C., during which3:5-bistrifluoromethyl-4-sulfonamidocarbanilide settles out. Onrecrystallization from acetonitn'le it melts at 228-230 C.

(14) 3:5-bistrifluoromethyl-4'-chlorothiocarbanilide is prepared asdescribed under (8) above. On recrystallization frombenzene-i-cyclohexane it melts at 150-151 C.

(15) A mixture of 17.8 grams of para-dimethylaminophenyl isothiocyanateand 22.9 grams of 3:5-bis-trifiuoromethylaniline is heated for severalhours on a boiling water bath. The reaction mixture is at first liquidand then, after a short time, it turns into a crystalline substancewhich is expressed on a suction filter;3:5-bis-trifluoromethyl-4-dimethylamino-thiocarbanilide is thenrecrystallized fiom benzene.

(16) A solution of 16.5 grams of para-aminobenzoic acid ethyl ester in15 cc. of acetonitrile is mixed with 27.1 grams of3:S-bis-trifluoromethylphenyl isothiocyanate. The temperature soon risesto 65 C. and shortly afterwards 3:5bis-trifiuoromethyl-4'-carbethoxy-thiocarbanilide settles out; it isdried under vacuum and then recrystallized from acetonitrilc, whereuponit melts at 147.5-148" C.

(17) A solution of 21.5 grams of thiocyananiline in cc. of acetonitrileis mixed with vigorous stirring with a solution of 36.5 grams of3:S-bis-trifluoromethylphenyl isocyanate in 30 cc. of acetonitrile. Thereaction mixture heats up to 50 C. On seeding,3:5-bis-trifluoromethyl-4- thiocyanocarbanilide is obtained in crystalswhich, on recrystallization from acetonitrile, melt at 204-205 C.

(18) A solution of 13.5 grams of para-aminoacetophenone in 100 cc. ofacetonitrile is vigorously stirred with a solution of 25.5 grams of3:5-bis-trifluoromethylphenyl isocyanate in 25 cc. of acetonitrile.3:5-bis-trifluoromethyl-4'-acetocarbanilide settles out within a fewseconds; it is suctioned off, recrystallized from butanol and washedwith acetonitrile, whereupon it melts at 238- 239 C.

(19) A solution of 11.8 grams of para-aminobenzonitrile in 100 cc. ofacetonitrile is mixed with a solution of 25.5 grams of3:S-bis-trifluoromethylphenyl isocyanate in 25 cc. of acetonitrile,whereupon 3:5-bis-trifluoromethyl-4'-cyanocarbanilide settles out aftersome time. His suctioned 0E and recrystallized from acetonitrile; itmelts at 252-253 C. r

(20) A solution of 27.8 grams of meta-methylthioaniline in 100 cc. ofacetonitrile is mixed with 51 grams of 3 :S-bis-trifluoromethylphenylisocyanate in acetonitrile.

3 z5 bis-trifiuoromethyl-3-thiomethylcarbanilide settles out onlyslowlyfrom the reaction mixture heated to 60 C.; it

is suctioned off, washed and recrystallized from acetoni onrecrystallization from benzeneel-cyclohexane it melts at (22) 3:5 bistrifluoromethyl 2':4':6-trichlorocarbanilide is obtained by condensationof 3:5-bis-trifluoromethylphenyl isocyanate and 2:4:6-trichloroanilinein acetouitrile at 60 C. The product melts at 225-227 C., thensolidifies again at 229 C. and sublimes at about 295 C.

(23) To a solution of 21.2 grams of 2-chloro-6-methylaniline in 100 cc.of acetonitrile are added dropwise 38.25 grams of3:5-bis-trifiuoromethylphenyl isocyanate, whereupon 3:5 bistrifluoromethyl 2' chloro-6'-methylcarbanilide settles outspontaneously. On recrystallization from acetonitrile it melts at 227 C.

(24) A solution of 10 grams of 2-methylsu1fonyl-4- nitraniline in 100cc. of dimethylformamide is mixed with 10 grams of3:5bis-trifluoromethylaniline and the batch is heated for 2 hours at 50C., then cooled, and 100 cc. of water are added. The precipitate soformed is filtered off and purified by crystallization from aqueousethanol, to yield 3z5bis-trifluoromethyl-2'-rnethylsulfonyl-4'-nitrocarbanilide in crystalsmelting at 227230 C.

(25) A solution of 10 grams of 2-ethylsulfonyl-5-trifiuoromethylanilinein 100 cc. of dimethylformamide is mixed with 10 grams of315bis-trifluoromethylphenyl isocyanate, and the whole is heated for 2hours at 50 C. On addition of water a crystalline product precipitateswhich is recrystallized from methylene chloride-l-petroleum ether, toyield crystalline 3:5-bis-trifluoromethyl-2'- ethylsulfonyl 5'trifluorornethylcarbanilide melting at 173-175 C.

(26) A solution of 10 grams of 2:6-dinitro-4-aminoanisole in 100 cc. ofdimethylformamide is mixed with 10 grams of 3 :bis-trifluoromethylphenylisocyanate, and the whole is heated for 2 hours at 50 C., then cooled,and 100 cc. of water are added. An oil settles out which crystallizesafter standing for some time. On recrystallization from aqueous ethanolthere is obtained crystalline 3:5bis-tn'fluoromethyl-3':5'-dinitro4-methoxycarbanilide melting at 226-228C.

(27) The thiocarbanilide used in the above examples may be prepared asfollows:

A solution of 5.0 grams of 4-nitro-am'line and 10.0 g. of3,5-bis-trifiuoromethylphenyl isothiocyanate in 50 cc. of acetonitrileis heated for 4 hours at 80 C. After cooling, 100 cc. of water is addedat room temperature, whereupon the 3:5bis-trifiuoromethyl-4'-nitro-thiocarbanilide precipitates. Afterrecrystallization from dimethylformamide-l-Water, it melts at 175-177 C.

From the above compounds, preparations can be made as shown, forexample, in Examples 1 or 2.

What is claimed is:

1. A pharmaceutical preparation containing a compound or" the formula Ion r -Q wherein R represents a member selected from the group consistingof lower alkyl, lower alkoxy, F, Cl, Br, I, -CF -NO CN, fiSO H, SO NH SOCH OH, SCN, SO NHA,

A S Or-N containing the 3,5-bis-trifiuoromethyl-4nitro thiocarbanilideof the formula wherein R represents a member selected from the groupconsisting of lower alkyl, lower alkoxy, F, Cl, Br, I, -CF NO CN, SO H,SO NH SO CH OH, ACN, SO NHA,

COOH, COCH COOA, CONH CONHA and CONA A standing for lower alkyl, n for awhole number from 1 to 4, and X for a member selected from the groupconsisting of O and S.

9. Method for the treatment of mammals infested by worms, comprisingadministering to the host, an anthelmintically effective amount of3,5-bis-trifluoromethyl-4'- nitro-carbanilide.

10. Method for the treatment of mammals infested by worms, comprisingadministering to the host, an anthelmintically effective amount of3,5-bis-trifluoromethyl-4'- nitro-thiocarbanilide.

11. Method for the treatment of mammals infested by Worms, comprisingadministering to the host a compound of the formula I X C F;

wherein R represents a member selected from the group consisting oflower alkyl, lower alkoxy, F, Cl, Br, I, CF NO -CN, SO H, SO NH SO CHOH, SCN, %O NHA,

/A SO2N\ COOH, COCH COOA, CONH CONHA and CONAg, A standing for loweralkyl, n for a whole number from 1 to 4, and X for a member selectedfrom the group consisting of O and S in a dosage of 25-2000 mg.

12. Method for the treatment of mammals infested by worms, comprisingadministering to the host,3,5-bis-trifluoromethyl-4'-nitro-thiocarbanilide in a dosage of 25- 2000mg.

13. Method for the treatment of mammals infested by worms, comprisingadministering to the host 3,5-bis-trifluoromethyl-4'-nitro-thiocarb2ini1ide in a dosage-of 25- References Cited 7 UNITED STATES PATENTS14. Method for the treatment of mammals infested by 5 8 75/1956 h 16 30worms, comprising administering to the host 3,5-bis-tri- 5/1961ilillllgromethyl 4 mm carbamhde m a dosage of 100- 00 5 3,073,861 H1963Ra'asch 16755 15. Method for the treatment of mammals infested by3,230,141 1/1966 v worms, comprising administering to the host3,5-bis-trifluoromethy1-4'-nitrothiocarbanilide in a dosage of 100- SAMROSEN Prlmary- Examiner 500 mg. JULIAN S. LEVITT, Examiner.

8.METHOD FOR THE TREATMENT OF MAMMALS INFESTED BY WORMS, COMPRISINGADMINISTERING TO THE HOST, AN ANTHELMINTICALLY EFFECTIVE AMOUNT OF ACOMPOUND OF THE FORMULA